“Real World” Assessment of Side Effects and Discontinuation Rates in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib

Ibrutinib is an orally administered Bruton tyrosine kinase inhibitor used in the treatment of patients with CLL. Because ibrutinib has been prescribed in the United States for several years, researchers sought to learn how the rates of side effects in the “real world” compared with those reported in clinical trials.

Ibrutinib (Imbruvica; Pharmacyclics), an oral first-generation Bruton tyrosine kinase inhibitor, was first approved for use in patients with chronic lymphocytic leukemia (CLL) in February 2014. According to data from clinical trials, which the FDA reviewed for the drug’s approval, ibrutinib was well-tolerated. Discontinuation of ibrutinib occurred in <9% of patients after 1 year of treatment in these clinical trials.

Knowing that ibrutinib has a role in the initial and subsequent treatment of patients with CLL, researchers wondered whether discontinuation rates for ibrutinib in the real world (eg, cancer centers, clinics, and doctors’ offices not involved in clinical trials) were different from rates reported in universities and other cancer centers that run clinical trials. They predicted that there would be a higher rate of ibrutinib discontinuation in older patients with CLL, and in patients whose overall physical condition, or “performance status,” was poor. Performance status is a measure of a patient’s ability to perform certain activities of daily living without help from others. Older patients and those with poor performance status are often underrepresented in clinical trials.

Researchers reviewed data from patients with CLL who were treated at one of more than 280 community cancer clinics in the United States. Data for all patients who received initial treatment for CLL between March 1, 2014, and February 28, 2019, were included in this analysis. These nationwide data were collected and managed by Flatiron Health, a company that analyzes anonymous information from the electronic health records of patients with cancer.

The results showed that by late 2018, approximately 40% of patients who required treatment for CLL started with ibrutinib. Among 1,497 patients, 16.2% stopped taking ibrutinib within 6 months. The rate of early discontinuation of ibrutinib was higher among patients aged ≥80 years (26.2%) compared with patients aged 60 to 70 years (9.4%). This rate was also higher among patients with a poor performance status (33.8%) versus patients with a good performance status (10.2%).

Researchers concluded that ibrutinib is being used more and more in the first-line setting for patients with CLL, but that early discontinuation of treatment is more likely in the real world than in pivotal clinical trials. These researchers look forward to the development of more effective decision support tools and cancer care delivery approaches to improve real-world patients’ ability to remain on ibrutinib therapy. In addition, researchers are seeking to identify other drugs that may be better tolerated by older patients or those with poor performance status.

The chemotherapy-free combination of venetoclax plus obinutuzumab has shown efficacy and tolerability in older patients with chronic lymphocytic leukemia. Adding acalabrutinib, a new targeted agent, may enhance the clinical benefits of this regimen, according to results of a clinical trial.

Alliance A041702 is a large clinical trial that is exploring whether adding venetoclax to the combination of ibrutinib and obinutuzumab can improve outcomes in patients with chronic lymphocytic leukemia.

According to results from a recent study, patients with chronic lymphocytic leukemia are more likely to survive for longer time periods if their posttreatment tests show no evidence of residual disease.

Last modified: February 12, 2020

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